Targeted Therapy for Leukemia

 描述（由申请人提供）：伯德转化实验室研究计划的重点是基础和转化生物学问题，以开发新的免疫和靶向治疗血液恶性肿瘤。慢性淋巴细胞白血病（CLL）被用作我们的疾病模型，因为它允许将自发性白血病小鼠模型中的机制和遗传研究与使用原发性肿瘤样本的研究相结合，从而增强我们发现的临床相关性。我们高度协作的实验室团队致力于识别、剖析和解决白血病治疗开发中的挑战，充分利用各自的优势，推动项目走向临床应用。它还使我们能够利用不同的技术（例如蛋白质组学，下一代测序），并开始新的领域（例如新型药物递送方法，靶标识别，引入新的动物模型），以将我们的发现转化为多种人类疾病。这一策略导致了强大的合作，从其他领域招募熟练的研究人员，将他们的知识应用于白血病。我设想我的研究的最大影响将来自于将靶向肿瘤生存途径的治疗方法与逆转免疫耐受以促进长期缓解或治愈的药物相结合。迄今为止，我的工作已经批准了两种用于CLL治疗的药物，可以延长生存期。我们正在进行的伊马替尼研究消除了一种普遍持有的范式，即当不存在特定的遗传畸变时，不可能开发出通用的“疾病靶向治疗”。我的假设是，一般的疾病靶向治疗需要双重肿瘤靶向和免疫调节。我寻求积极发展这一概念，并根据我们的数据指导我们将其扩展到其他领域。

 DESCRIPTION (provided by applicant): The Byrd translational laboratory research program focuses on basic and translational biologic questions to develop novel immunologic and targeted therapies for hematologic malignancies. Chronic lymphocytic leukemia (CLL) is utilized as our disease model as it allows integration of mechanistic and genetic studies in spontaneous leukemia mouse models with studies using primary tumor samples, thereby enhancing the clinical relevance of our findings. Our highly collaborative laboratory team works to identify, dissect, and solve challenges in leukemia therapeutic development that capitalizes on the strengths of each to drive projects to clinical application. It also allows us to exploit diverse techniques (e.g. proteomics, next-generation sequencing) and embark on new areas (e.g. novel drug delivery methods, target identification, introduction of new animal models) to translate our findings across multiple human diseases. This strategy has resulted in powerful collaborations, recruiting skilled researchers from other fields to apply their knowledge to leukemia. I envision the greatest impact from my research will come from integrating therapeutics that target tumor survival pathways with agents that reverse immune tolerance to facilitate long-term remissions or cure. My work to date has resulted in the approval of two agents for CLL therapy that prolong survival. Our ongoing work with imbrutinib dispels a commonly held paradigm that it is not possible to develop a general "disease-targeted therapy" when a specific genetic aberration is not present. My hypothesis is that general disease-targeted therapy requires dual tumor-targeted and immunologic modulation. I seek to aggressively develop this concept and extend it to other areas as our data directs us.